Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro

Ru Feng Wu; Cheng Xu Liao; Shuhei Tomita; Yoshiyuki Ichikawa; Lance S. Terada

doi:10.1016/j.lfs.2004.02.018

Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro

Ru Feng Wu, Cheng Xu Liao, Shuhei Tomita, Yoshiyuki Ichikawa, Lance S. Terada

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7 Scopus citations

Abstract

Lidocaine, bupivacaine and propranolol are amines that can be expected to act as substrates for FAD-containing monooxygensae (FMO) (EC 1. 14. 13. 8). We found that FMO metabolizes lidocaine, bupivacaine and propranolol. The Km and Vmax values of lidocaine, bupivacaine and propranolol for FMO are 143, 408 and 210 μM, and 145, 119 and 135 nmol/min/mg FMO protein, respectively. The lipophilicity of the drugs decreased in the following order: lidocaine>propranolol>bupivacaine, under our experimental conditions. Furthermore, the metabolic products of FMO were separated by high-performance liquid chromatography and analyzed by gas chromatography-mass spectrometry, and were found to be the N-oxides and N-hydroxylamines of the respective drugs. These findings suggest that lidocaine, bupivacaine and propranolol are substrates for FMO, and the enzymatic toward lidocaine or bupivacaine may be inhibited exclusively and competitively by propranolol.

Original language	English (US)
Pages (from-to)	1011-1019
Number of pages	9
Journal	Life Sciences
Volume	75
Issue number	8
DOIs	https://doi.org/10.1016/j.lfs.2004.02.018
State	Published - Jul 9 2004

Keywords

Bupivacaine
FAD-containing monooxygenase
Lidocaine
Propranolol
β-adrenergic-blocking reagent

ASJC Scopus subject areas

General Pharmacology, Toxicology and Pharmaceutics
General Biochemistry, Genetics and Molecular Biology

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10.1016/j.lfs.2004.02.018

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title = "Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro",

abstract = "Lidocaine, bupivacaine and propranolol are amines that can be expected to act as substrates for FAD-containing monooxygensae (FMO) (EC 1. 14. 13. 8). We found that FMO metabolizes lidocaine, bupivacaine and propranolol. The Km and Vmax values of lidocaine, bupivacaine and propranolol for FMO are 143, 408 and 210 μM, and 145, 119 and 135 nmol/min/mg FMO protein, respectively. The lipophilicity of the drugs decreased in the following order: lidocaine>propranolol>bupivacaine, under our experimental conditions. Furthermore, the metabolic products of FMO were separated by high-performance liquid chromatography and analyzed by gas chromatography-mass spectrometry, and were found to be the N-oxides and N-hydroxylamines of the respective drugs. These findings suggest that lidocaine, bupivacaine and propranolol are substrates for FMO, and the enzymatic toward lidocaine or bupivacaine may be inhibited exclusively and competitively by propranolol.",

keywords = "Bupivacaine, FAD-containing monooxygenase, Lidocaine, Propranolol, β-adrenergic-blocking reagent",

author = "Wu, {Ru Feng} and Liao, {Cheng Xu} and Shuhei Tomita and Yoshiyuki Ichikawa and Terada, {Lance S.}",

year = "2004",

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doi = "10.1016/j.lfs.2004.02.018",

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T1 - Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro

AU - Wu, Ru Feng

AU - Liao, Cheng Xu

AU - Tomita, Shuhei

AU - Ichikawa, Yoshiyuki

AU - Terada, Lance S.

PY - 2004/7/9

Y1 - 2004/7/9

N2 - Lidocaine, bupivacaine and propranolol are amines that can be expected to act as substrates for FAD-containing monooxygensae (FMO) (EC 1. 14. 13. 8). We found that FMO metabolizes lidocaine, bupivacaine and propranolol. The Km and Vmax values of lidocaine, bupivacaine and propranolol for FMO are 143, 408 and 210 μM, and 145, 119 and 135 nmol/min/mg FMO protein, respectively. The lipophilicity of the drugs decreased in the following order: lidocaine>propranolol>bupivacaine, under our experimental conditions. Furthermore, the metabolic products of FMO were separated by high-performance liquid chromatography and analyzed by gas chromatography-mass spectrometry, and were found to be the N-oxides and N-hydroxylamines of the respective drugs. These findings suggest that lidocaine, bupivacaine and propranolol are substrates for FMO, and the enzymatic toward lidocaine or bupivacaine may be inhibited exclusively and competitively by propranolol.

AB - Lidocaine, bupivacaine and propranolol are amines that can be expected to act as substrates for FAD-containing monooxygensae (FMO) (EC 1. 14. 13. 8). We found that FMO metabolizes lidocaine, bupivacaine and propranolol. The Km and Vmax values of lidocaine, bupivacaine and propranolol for FMO are 143, 408 and 210 μM, and 145, 119 and 135 nmol/min/mg FMO protein, respectively. The lipophilicity of the drugs decreased in the following order: lidocaine>propranolol>bupivacaine, under our experimental conditions. Furthermore, the metabolic products of FMO were separated by high-performance liquid chromatography and analyzed by gas chromatography-mass spectrometry, and were found to be the N-oxides and N-hydroxylamines of the respective drugs. These findings suggest that lidocaine, bupivacaine and propranolol are substrates for FMO, and the enzymatic toward lidocaine or bupivacaine may be inhibited exclusively and competitively by propranolol.

KW - Bupivacaine

KW - FAD-containing monooxygenase

KW - Lidocaine

KW - Propranolol

KW - β-adrenergic-blocking reagent

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Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro

Abstract

Keywords

ASJC Scopus subject areas

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